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Abstract

Caveolin-1 (CAV1) is a membrane protein involved in essential cellular processes such as endocytosis, signal transduction, and lipid metabolism, with complex and context-dependent roles in cancer. This study provides the first comprehensive pan-cancer and pan-tissue analysis of CAV1-associated gene and protein networks by integrating transcriptomic data from GTEx and TCGA with proteomic data from CPTAC. We reveal both conserved and cancer-specific co- expression patterns, identifying tumor-specific shifts in gene correlations with CAV1 that highlight distinct biological pathways including immune signaling, extracellular matrix remodeling, and cytoskeletal organization. From these findings, we derived a tumor-enhanced, immune-related 4-gene signature that robustly predicts overall survival in colon cancer patients with high CAV1 expression, with validation in an independent proteomic cohort. Single-cell RNA sequencing further localized CAV1 and its co-expressed partners primarily to immune cells and cancer-associated fibroblasts within the tumor microenvironment, underscoring their potential roles in tumor progression and immune modulation. By uncovering genes with tumor- enhanced and tumor-reduced correlations, this work identifies promising prognostic markers that may inform survival outcomes in cancers characterized by variable CAV1 expression. Overall, our findings deepen the understanding of CAV1’s multifaceted functions in cancer and offer valuable insights that could guide future research in precision oncology.